cancer cell metabolism

This is an article which has very important long term interest for Nutrition.
Good cells perform their physiological activities at the right time and place. When removed from their natural surroundings they self-destruct,called anoikis . Cancer cells: however they survive, invade other tissues and continue to grow in unfamiliar territories. Schafer et al in Nature 2009 vol 461 pp 109-113 show that cancer-inducing oncogenes may protect cells from anoikis by maintaining the cells glucose consumption. Death of normal cells remote from their normal site is caused by starvation, and strongly connects cellular metabolism to cancer.
Anoikis occurs when cells detach from the basement membrane or the extracellular matrix, both of which provide them with survival signals Originally, anoikis was thought to be .executed by apoptosis – a programmed cell death set off by several different cues, which results in cell fragmentation and elimi¬nation. But blocking apoptosis does not prevent anoikis because detached cells die anyway. Moreover, another process, autophagy – in which the cell digests some of its own components is observed in anoikic cells. If autophagy runs its full course, cells kill themselves by self-consumption but, initially autophagy may help cells to survive starvation.
Cancer cells have an unbridled capacity for proliferation and invasion. Thus cancer cels escape anoikis , or anoikis prevents cancer. Several oncogenes hinder anoikis but the mechanism is obscure.
One oncogene ERBB2 encodes the epidermal growth factor receptor , a cell surface protein that is activated in 25% of breast cancers. Schafer et al. show that ERBB2 expression rescues detached cells from energy depletion by maintaining their glucose uptake, specifically by activating the cancer-inducing P13K/AKT pathway.
Once in the cell, glucose may be metabolized through several pathways, including glycolysis, in which it is broken down to pyruvate to generate ATP, the cell’s energy currency, and NADH, a mediator of ATP production. Pyruvate is routed to the mitochondria where, in the presence of oxygen, it is metabolized to produce large amounts of ATP . Although oxygen is essential for generating the maximum yield of energy from glucose breakdown, it can also fatally damage the cell by contributing to various forms of oxidative stress. Glucose helps to prevent this oxidative stress by bypassing the initial steps of glycolysis and enters the pentose phosphate pathway. This produces less ATP but generates NADPH, a powerful mediator of antioxidative reactions that protect cells from oxidative damage.
Schafer et al. note that anoikis can be prevented in normal, detached, glucose-starved.cells if they are given antioxidants’ showing that it is increased oxidative stress rather than decreased glycolysis that induces rapid anoikis.

Gotttlieb et al 2009 The fat and furious Nature vol 461 p 44-5

Schafer et al 2009Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment Nature vol 461 109-113.

Martin Eastwood
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